1. Field of the Invention
The present invention is directed to an improved process for the preparation of .alpha.-alkyl-lactones. The process involves reacting an .alpha.-acyl lactone, an aldehyde and an alkali metal hydroxide in a suitable diluent to form the .alpha.-alkylidene lactone and then hydrogenating to obtain the corresponding .alpha.-alkyl-substituted product.
2. Description of the Prior Art There has been considerable interest in the preparation of .alpha.-alkylidene lactones and their saturated analogues, i.e. .alpha.-alkyl lactones. Various .UPSILON.-butyrolactones having alkyl substituents in the .alpha.-position are reported to have flower- or fruit-like aromas.
Synthetic routes to the .alpha.-alkylidene-substituted products generally involve either (a) formation of the .alpha.-methylene or .alpha.-alkylidene lactone from acyclic precursors containing all of the desired functional groups via a ring closure reaction; or (b) conversion of an existing group at the .alpha.-position on a preformed lactone ring to the corresponding .alpha.-methylene or .alpha.-alkylidene group. The .alpha.-alkylidene derivative can then conveniently be hydrogenated to the corresponding .alpha.-alkyl lactone. The present invention is directed to a process wherein the hydrogen and acetyl groups present in the .alpha.-position of a lactone ring are first removed and replaced with an .alpha.-alkylidene moiety and the .alpha.-alkylidene group is then hydrogenated (reduced) to produce an .alpha.-alkyl-.UPSILON.-butyrolactone or .alpha.-alkyl-.delta.-valerolactone.
Numerous methods for the synthesis of .alpha.-methylene lactones are discussed in the review articles of P. A. Greico (Synthesis 1975, 67) and N. Petragnani et al. (Synthesis 1986, 157). None of the reactions described in either reference, however, deal with the preparation of .alpha.-alkylidene lactones. In fact, there is only one mention of the reaction of an acetyl group which is substituted at the .alpha.-position. Ueno et al (Tetrahedron Lett. 1978, 3753) describe the reaction of .alpha.-acetyl-.gamma.-butyrolactone with paraformaldehyde, lithium diisopropylamide in tetrahydrofuran to produce .alpha.-methylene-.gamma.-butyrolactone.
Ksander et al in J. Org. Chem. 1977, 42, 1180 describe the preparation of .alpha.-alkylidene lactones by the reaction of ethyl oxalylbutyrolactones, with an aldehyde in the presence of aqueous sodium hydroxide. There is no suggestion by Ksander et al to the use of .alpha.acyl-substituted lactones of any type for the reaction.
Ono et al (J. Org. Chem. 1983, 48, 3678) report the conversion of an ester group which is substituted at the .alpha.-position on a .gamma.-butyrolactone ring to an .alpha.-isopropylidene moiety. The complex multi-step process involves reaction of the carbanion of an .alpha.-carboethoxy-.gamma.-butyrolactone and 2-chloro-2-nitropropane in the presence of a 150-watt tungsten lamp followed by the addition of sodium bromide and heat. In the only situation where Ono et al utilize a ring structure having an acetyl group in the .alpha.-position, namely, 2-acetylcyclopentanone, the corresponding .alpha.-isopropylidene cyclopentanone is not produced.
A multi-step synthesis which involves formylating an .alpha.-lactone using sodium hydride and ethyl formate and then condensing the resulting enolate with an aldehyde to obtain the corresponding .alpha.-methylene-.gamma.-lactone is reported by Murray et al in J.Chem.Soc., Chem, Commun., 1984 at pp. 132-133.
Various procedures for hydrogenating unsaturated hydrocarbon substituents on lactone or other ring systems are known. It would be highly useful if a process were available wherein the acyl substituent on a lactone could be readily replaced by an alkylidene moiety which in turn could be hydrogenated to produce the corresponding alkyl-substituted lactone. These and other advantages are realized with the process of the present invention which will be described in more detail to follow.